The mouse RACK1 gene is regulated by nuclear factor-κB and contributes to cell survival

The mouse RACK1 gene is regulated by nuclear factor-κB and contributes to cell survival
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DOI:
10.1124/mol.64.6.1541
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发表时间:
2003-12-01
影响因子:
3.6
通讯作者:
Messing, RO
Messing, RO
中科院分区:
医学3区
文献类型:
--
作者:
Choi, DS;Young, H;Messing, RO

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活化C激酶受体1(RACK 1)是一种多功能的、含有WD基序的蛋白质,在调节多种细胞表面受体和细胞内蛋白激酶方面很重要。为了更好地了解其功能,我们克隆了小鼠RACK 1基因,发现它包含8个外显子和7个内含子,并定位于小鼠染色体11B1.2-1.3。启动子分析确定NF-κ B作为启动子活性的重要转录因子。在PC-12细胞中,激活核因子-κ B(NF-kappaB)的神经生长因子(NGF)在无血清培养基中维持RACK 1水平并促进细胞存活。NF-kappaB激活抑制剂阻断了NGF刺激的存活和RACK 1表达,而RACK 1的转基因表达促进了缺乏血清和NGF的细胞的存活。因此,RACK 1基因表达由NF-κ B诱导,RACK 1有助于NF-κ B介导的细胞存活。
Receptor for activated C kinase 1 (RACK1) is a multifunctional, WD motif-containing protein important in regulating several cell surface receptors and intracellular protein kinases. To better understand its function, we cloned the mouse RACK1 gene and found it contains eight exons and seven introns, and maps to mouse chromosome 11B1.2-1.3. Promoter analysis identified NF-kappaB as an important transcription factor for promoter activity. In PC-12 cells, nerve growth factor (NGF), which activates nuclear factor-kappaB (NF-kappaB), maintained RACK1 levels and promoted cell survival in serum-free medium. Inhibitors of NF-kappaB activation blocked NGF-stimulated survival and RACK1 expression, whereas transgenic expression of RACK1 promoted survival in cells deprived of serum and NGF. Thus, RACK1 gene expression is induced by NF-kappaB and RACK1 contributes to NF-kappaB-mediated cell survival.